Endoscopic Therapy vs Surveillance for Barrett's Esophagus

(SURVENT Trial)

Recruiting at 22 trial locations

Overseen By Sandra Boimbo

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Colorado, Denver

Must be taking: Proton pump inhibitors

Must not be taking: Antiplatelets, Anticoagulants

Disqualifiers: Pregnancy, Prior eradication therapy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 3.5 years

680 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The purpose of this study is to learn the best approach to treating patients with known or suspected Barrett's esophagus by comparing endoscopic surveillance to endoscopic eradication therapy. To diagnose and manage Barrett's esophagus and low-grade dysplasia, doctors commonly use procedures called endoscopic surveillance and endoscopic eradication therapy. Endoscopic surveillance is a type of procedure where a physician will run a tube with a light and a camera on the end of it down the patients throat and remove a small piece of tissue. The piece of tissue, called a biopsy, is about the size of the tip of a ball-point pen and is checked for abnormal cells and cancer cells. Endoscopic eradication therapy is a kind of surgery which is performed to destroy the precancerous cells at the bottom of the esophagus, so that healthy cells can grow in their place. It involves procedures to either remove precancerous tissue or burn it. These procedures can have side effects, so it is not certain whether risking those side effects is worth the benefit people get from the treatments. While both of these procedures are widely accepted approaches to managing the condition, there is not enough research to show if one is better than the other. Barrett's esophagus and low-grade dysplasia does not always worsen to high-grade dysplasia and/or cancer. In fact, it usually does not. So, if a patient's dysplasia is not worsening, doctors would rather not put patients at risk unnecessarily. On the other hand, endoscopic eradication therapy could possibly prevent the worsening of low-grade dysplasia into high-grade dysplasia or cancer (esophageal adenocarcinoma) in some patients. Researchers believe that the results of this study will help doctors choose the safest and most effective procedure for their patients with Barrett's esophagus and low-grade dysplasia. This is a multicenter study involving several academic, community and private hospitals around the United States. Up to 530 participants will be randomized. This study will also include a prospective observational cohort study of up to 150 Barrett's esophagus and low grade dysplasia patients who decline randomization in the randomized control trial but undergo endoscopic surveillance (Cohort 1) or endoscopic eradication therapy (Cohort 2), and are willing to provide longitudinal observational data.

Will I have to stop taking my current medications?

The trial requires participants to stop taking antiplatelet and anticoagulant medications before and after endoscopic procedures, based on standard guidelines. It does not specify other medications, so you may not need to stop taking them.

Is endoscopic eradication therapy (EET) safe for humans?

Several studies have shown that endoscopic eradication therapy (EET) is generally safe for treating Barrett's esophagus, a condition that can lead to esophageal cancer. The therapy is widely used and recommended by medical societies for managing this condition. ^{1 2 3 4 5}

How is endoscopic eradication therapy different from other treatments for Barrett's esophagus?

Endoscopic eradication therapy (EET) is unique because it directly targets and removes abnormal cells in the esophagus using an endoscope (a flexible tube with a camera and tools), aiming to completely eradicate the precancerous condition known as Barrett's esophagus. Unlike other treatments that may focus on managing symptoms or preventing acid reflux, EET actively removes the problematic tissue, reducing the risk of progression to cancer. ^{2 4 5 6 7}

What data supports the effectiveness of the treatment Endoscopic Eradication Therapy for Barrett's Esophagus?

Research shows that Endoscopic Eradication Therapy (EET) is effective in treating Barrett's Esophagus by achieving complete eradication of abnormal cells, which can help prevent the progression to cancer. Studies indicate that EET is the standard care for Barrett's Esophagus-related neoplasia, with an average of three sessions needed to achieve complete eradication. ^{2 4 5 6 7}

Who Is on the Research Team?

Sachin Wani, MD

Principal Investigator

University of Colorado, Denver

Nicholas J. Shaheen

Principal Investigator

University of North Carolina

Valerie Durkalski, MPH, PhD

Principal Investigator

Medical University of South Carolina

Rhonda Souza, MD

Principal Investigator

Baylor University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Barrett's esophagus and low-grade dysplasia, who can tolerate acid-reducing medication and stop blood thinners before endoscopic procedures. It excludes those with high-grade dysplasia or cancer, active severe esophagitis, short life expectancy, pregnancy, prior surgery or treatment on the esophagus, and certain esophageal conditions.

Inclusion Criteria

I have Barrett's esophagus with low grade dysplasia and agree to participate.

My biopsy from the last year shows Barrett's esophagus with low grade dysplasia.

My biopsy from the last year shows low grade dysplasia.

Exclusion Criteria

Life expectancy of <2 years as judged by the site investigator

I have had surgery to remove part or all of my esophagus.

Pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo either endoscopic eradication therapy or endoscopic surveillance based on randomization

3.5 years

Every 2-3 months for eradication therapy; every 6 months for surveillance

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Semi-annual follow-up calls

Long-term Follow-up

Continued monitoring of participants for progression to high-grade dysplasia or cancer

Until study completion

What Are the Treatments Tested in This Trial?

Interventions

• Endoscopic Eradication Therapy

Trial Overview The study compares two methods for managing Barrett's esophagus: 'endoscopic surveillance' (monitoring through a camera-tube down the throat) versus 'endoscopic eradication therapy' (surgery to remove or destroy precancerous cells). Up to 530 participants will be randomly assigned to either method in various U.S. hospitals.

How Is the Trial Designed?

Group I: Endoscopic Eradication Therapy Experimental Treatment 1 Intervention

Subjects undergoing endoscopic eradication therapy will undergo radiofrequency ablation every 2-3 months until complete eradication of intestinal metaplasia (CE-IM) is achieved or 5 treatments have been delivered, whichever is first. After achieving CE-IM, surveillance endoscopy will performed every 6 months for the first year and annually thereafter until the end of the study period. Surveillance biopsies will be obtained using a standardized protocol.

Group II: Endoscopic Surveillance Active Control 1 Intervention

Subjects in the randomized control trial and observational cohort study, undergoing surveillance endoscopy will undergo surveillance biopsies in a 4-quadrant fashion every 1 cm throughout the extent of the Barrett's esophagus using the Seattle biopsy protocol, along with targeted biopsies from any visible lesions. For incident low grade dysplasia (newly diagnosed low grade dysplasia - within 12 months of enrollment), surveillance endoscopies will be performed every 6 months for the first year and then annually until the end of the study period. For prevalent low grade dysplasia (diagnosed \>1 year prior to enrollment), surveillance endoscopies will be performed annually until the end of the study period. The number of evaluations will depend on a subject's enrollment time.

Endoscopic Eradication Therapy is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Endoscopic Eradication Therapy for:

• Barrett's esophagus with dysplasia
• Early neoplasia

Approved in United States as Endoscopic Eradication Therapy for:

• Barrett's esophagus with dysplasia
• Early esophageal adenocarcinoma

Approved in Canada as Endoscopic Eradication Therapy for:

• Barrett's esophagus with dysplasia
• Early neoplasia

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Baylor University

Collaborator

Trials

65

Recruited

67,600+

University of North Carolina

Collaborator

Trials

174

Recruited

1,457,000+

Medical University of South Carolina

Collaborator

Trials

994

Recruited

7,408,000+

Published Research Related to This Trial

Endoscopic eradication therapy (EET) is an effective and safe treatment for managing Barrett's oesophagus related neoplasia, aiming for complete eradication of intestinal metaplasia and subsequent surveillance for recurrence.

EET is now considered the standard of care for high-grade dysplasia and intramucosal carcinoma, while for low-grade dysplasia, both surveillance and ablation are viable options depending on individual patient factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endoscopic eradication therapy for Barrett's oesophagus: state of the art. Kolb, JM., Wani, S.[2022]

In a study of 4114 Barrett's esophagus patients undergoing endoscopic eradication therapy (EET), the overall incidence of esophageal adenocarcinoma (EAC) was low at 6.01 per 1000 person-years, particularly among patients with high-grade dysplasia (HGD) where it was 12.9 per 1000 person-years.

The study also found that the all-cause mortality rate was 13.23 per 1000 person-years, with the highest rates in patients already diagnosed with EAC (25.1 per 1000 person-years), and the need for esophagectomy was less than 1% across all dysplasia grades, indicating a favorable safety profile for EET in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence of Esophageal Adenocarcinoma, Mortality, and Esophagectomy in Barrett's Esophagus Patients Undergoing Endoscopic Eradication Therapy. Smith, ZL., Thorgerson, AM., Dawson, AZ., et al.[2023]

In a study of 623 patients with Barrett's esophagus undergoing endoscopic eradication therapy (EET), the average number of sessions required to achieve complete eradication of intestinal metaplasia (CE-IM) was found to be approximately 2.9, with 73% of patients achieving CE-IM after three sessions.

Age and the length of Barrett's esophagus were identified as significant predictors of incomplete response to EET, suggesting that alternative therapies may be necessary for patients who do not respond adequately after three sessions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Threshold evaluation for optimal number of endoscopic treatment sessions to achieve complete eradication of Barrett's metaplasia. Mittal, C., Muthusamy, VR., Simon, VC., et al.[2022]

Endoscopic eradication therapy is effective for treating Barrett's esophagus (BE) related neoplasia, but patients still need regular surveillance due to the risk of recurrence, with emerging evidence suggesting less frequent exams in the first year after successful treatment.

Future management may benefit from targeted biopsies and new technologies, such as biomarkers and personalized surveillance intervals, to improve efficiency and patient outcomes in monitoring for BE recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Post Ablative Barrett's Esophagus: a Review of Current Practices and Look at Emerging Technologies. Davis, C., Kolb, JM.[2023]

Endoscopic eradication therapy, particularly radiofrequency ablation (RFA), has shown excellent effectiveness in eradicating dysplasia in Barrett's esophagus, but there is a risk of recurrence, especially at the gastroesophageal junction, influenced by factors like the length of Barrett's segments and ongoing gastroesophageal reflux.

Recent advancements include combining RFA with endoscopic mucosal resection and new cost-effectiveness data indicating that RFA is economically viable for treating high-grade and low-grade dysplasia, but not for nondysplastic Barrett's esophagus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endoscopic eradication therapy for mucosal neoplasia in Barrett's esophagus. Dunbar, KB.[2018]

Endoscopic eradication therapy (EET) is a cost-effective treatment for patients with low and high grade dysplasia in Barrett's oesophagus, with an incremental cost-effectiveness ratio of £3006 per quality adjusted life year (QALY) gained.

The analysis indicates that EET becomes increasingly cost-effective over time, with a projected financial impact of £7.1 million on the UK National Health Service over five years, supporting its implementation based on updated guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A cost-effectiveness analysis of endoscopic eradication therapy for management of dysplasia arising in patients with Barrett's oesophagus in the United Kingdom. Pollit, V., Graham, D., Leonard, C., et al.[2020]

Achieving complete remission of intestinal metaplasia (CRIM) after endoscopic eradication therapy (EET) significantly reduces the risk of dysplasia and advanced neoplasia recurrence compared to achieving only complete remission of dysplasia (CR-D), with a risk ratio of 2.8 for dysplasia recurrence after CR-D.

In a systematic review of 40 studies involving 4410 patients, the cumulative incidence of dysplasia recurrence was 5% after CRIM and 12% after CR-D, highlighting the importance of targeting CRIM as the primary goal of EET for dysplastic Barrett's esophagus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Persistent intestinal metaplasia after endoscopic eradication therapy of neoplastic Barrett's esophagus increases the risk of dysplasia recurrence: meta-analysis. Sawas, T., Alsawas, M., Bazerbachi, F., et al.[2019]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Endoscopic eradication therapy for Barrett's oesophagus: state of the art. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Incidence of Esophageal Adenocarcinoma, Mortality, and Esophagectomy in Barrett's Esophagus Patients Undergoing Endoscopic Eradication Therapy. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

Threshold evaluation for optimal number of endoscopic treatment sessions to achieve complete eradication of Barrett's metaplasia. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Management of Post Ablative Barrett's Esophagus: a Review of Current Practices and Look at Emerging Technologies. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Endoscopic eradication therapy for mucosal neoplasia in Barrett's esophagus. [2018]

6. England pubmed.ncbi.nlm.nih.gov

A cost-effectiveness analysis of endoscopic eradication therapy for management of dysplasia arising in patients with Barrett's oesophagus in the United Kingdom. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Persistent intestinal metaplasia after endoscopic eradication therapy of neoplastic Barrett's esophagus increases the risk of dysplasia recurrence: meta-analysis. [2019]